FDA grants fast review for Roche's Tecentriq in tough-to-treat Triple Negative Breast cancer

Roche/Genentech’s new drug Tecentriq (atezolizumab) wins FDA priority review as a part of the regimen for the treatment of tough-to-treat Triple Negative Breast Cancer (TNBC). The drug will be used in combination with Celgene chemo med Abraxane (nab-paclitaxel) in previously untreated patients whose tumors express biomarker PD-L1.

A Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease.

Triple-negative breast cancer is the term used to describe breast cancers that lack estrogen- and progesterone-receptor expression and do not overexpress human epidermal growth factor receptor 2 (HER2). It is more aggressive and harder to treat, it is also more likely to spread and recur. Approximately 15% of breast cancers are triple-negative based on the results of diagnostic tests.

The company’s supplemental Biologics License Application (sBLA) is based on the results of phase III IMpassion130 study, involving 902 patients with advanced breast cancer. The results demonstrated that Tecentriq plus nab-paclitaxel as an initial (first-line) treatment for unresectable locally advanced or metastatic TNBC increased the median progression-free survival (PFS) to 7.2 months instead of 5.0 months as compared to nab-paclitaxel alone group. In a subgroup analysis of PD-L1-positive population, the median survival was further increased to 7.5 months vs. 5.0 months.

The drug combination improved clinically meaningful overall survival in the PD-L1-positive population (25.0 months vs. 15.5 months). The safety profile of the drug combination was as per that reported for individual drugs. Currently, Genentech has seven ongoing phase III studies investigating Tecentriq in patients who are in various stages of TNBC.

The results of the study were presented at the European Society for Medical Oncology (ESMO) Congress and published in the October issue of New England Journal of Medicine.

“Tecentriq in combination with nab-paclitaxel has the potential to meaningfully advance treatment for people with PD-L1-positive, metastatic triple-negative breast cancer. People need more options for this type of breast cancer, which is particularly difficult to treat,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We are working closely with the FDA to bring this Tecentriq combination to people with PD-L1-positive, metastatic triple-negative breast cancer as soon as possible.”

It is expected that FDA will give its decision on approval by March 12, 2019. If approved, this will be the first cancer immunotherapy regimen for the treatment of PD-L1-positive, metastatic TNBC. 

Genentech press release

Full Text-New England Journal of Medicine

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FDA approves the first new drug for the treatment of Influenza in nearly 2 decades

The U.S. Food and Drug Administration (FDA) today approved Roche Xofluza ™ (baloxavir marboxil) for the treatment of acute uncomplicated influenza (flu) in patients 12 years of age and older who have been symptomatic for no more than 48 hours.

 “This is the first new antiviral flu treatment with a novel mechanism of action approved by the FDA in nearly 20 years. With thousands of people getting the flu every year, and many people becoming seriously ill, having safe and effective treatment alternatives is critical. This novel drug provides an important, additional treatment option,” said FDA Commissioner Scott Gottlieb, M.D. “While there are several FDA-approved antiviral drugs to treat flu, they are not a substitute for yearly vaccination. Flu season is already well underway, and the U.S. Centers for Disease Control and Prevention recommends getting vaccinated by the end of October, as seasonal flu vaccine is one of the most effective and safest ways to protect yourself, your family and your community from the flu and serious flu-related complications, which can result in hospitalizations. Yearly vaccination is the primary means of preventing and controlling flu outbreaks.”

Influenza is a severe infectious disease worldwide with annual epidemics of 3 to 5 million cases of severe disease, millions of hospitalizations and up to 650,000 deaths worldwide.

Xofluza is a first-in-class, single-dose oral medicine and acts by inhibiting the polymerase acidic endonuclease, an enzyme essential for viral replication. It has shown efficacy against a wide range of influenza viruses, including oseltamivir-resistant strains and avian strains (H7N9, H5N1) in non-clinical studies.

The safety and efficacy of this single dose, antiviral drug Xofluza, was proved by the results of two randomized controlled clinical trials of 1,832 patients recently published in the 6 September 2018 issue of the New England Journal of Medicine. In phase III CAPSTONE-1 trial, participants were randomized to receive either Xofluza, a placebo, or another antiviral flu treatment within 48 hours of experiencing flu symptoms.

Xofluza significantly reduced the duration of flu symptoms by more than one day (median time 54 hours versus 80 hours; p<0.001) as compared to placebo. The efficacy was comparable to oseltamivir when it comes to duration of symptoms, but Xofluza significantly reduced the viral load 1 day after the start of therapy.

In the other phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P<0.05).

Thus, single-dose baloxavir was superior to placebo in alleviating influenza symptoms and was superior to both oseltamivir and placebo in reducing the viral load one day after initiation of the trial regimen in patients with uncomplicated influenza.

The most common adverse reactions in patients taking Xofluza included diarrhea and bronchitis, nausea, common cold symptoms (nasopharyngitis) and headache.

 FDA approved Xofluza under priority review, and the drug will be available across the U.S. in the coming weeks. Xofluza was discovered by Japanese drug maker Shionogi & Co., Ltd and was its 10mg/20mg tablets were approved by the Ministry of Health, Labour and Welfare in Japan in February 2018 for the treatment of Influenza Types A and B. 

The drug is being further developed and commercialized globally in collaboration with the Roche Group (which includes Genentech in the US). Under the terms of this agreement, Roche holds worldwide rights to Xofluza excluding Japan and Taiwan, which will be retained exclusively by Shionogi & Co., Ltd.

FDA press release

Roche press release

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FDA approves Roche’s COBAS HPV Test for use with SurePath Preservative Fluid.

  

The SurePath kit for collecting and transporting the cervical specimens.  

Clinical pearls:

• HPV testing can now be performed on samples collected for liquid based pap test in the BD SurePath preservation fluid using the SurePath vial. 
• Before the approval, healthcare providers have to collect two different samples in two different collecting fluids according to the specification of the testing labs.
• It is not approved as a first line primary screening test.

The U.S. FDA today approved the Roche COBAS test as the first test for Human Papilloma Virus(HPV) from cervical samples collected for Pap Test in BD SurePath Preservative fluid.[1]

COBAS HPV test is a qualitative in vitro test for the detection of Human Papillomavirus in patient specimens. The test utilizes amplification of target DNA by the Polymerase Chain Reaction (PCR) and nucleic acid hybridization for the detection of 14 high-risk (HR) HPV types in a single analysis.

BD SurePath is a liquid based pap test and the test pack includes collection kit, along with storage and transportation components with a vial of preservative liquid.

Some other properties of BD SurePath liquid-based Pap test are ease of transportation, have less than 24% Ethanol which results in immediate and complete cell fixation, preserving the morphology. It also has the ability to preserve the sample for 4 weeks at room temperature, 6 weeks refrigerated.[2]    

The kit comes with specific instructions on how to collect samples to minimize the risks of false negative results.

Till date FDA has not approved any HPV test that can be used with the preservation liquids. Healthcare providers have to collect two different samples, in two different collecting fluids before the announcement was made.

Now, a single sample collected can be used for carrying out both the tests. The test has been approved in women 21 years and more, and helps to determine additional follow-up and diagnostic procedures after ASC-US (Atypical Squamous Cells of Undetermined Significance) Pap cytology results. It has also been approved for use is patients 30 years and older as a primary screening test for HPV along with pap cytology. It detects 14 high-risk HPV types, including HPV 16 and 18, which are responsible for causing 70% of cervical cancer worldwide.

According to the National Cancer Institute, there will be an estimated 12,990 new cases and 4,120 deaths from cervical cancer in the United States during 2016.[3]

"Many labs have a preference in how samples are collected for processing, and this additional approval gives them another clinically validated option for the Cobas HPV test," Uwe Oberlaender, head of Roche Molecular Diagnostics, said in a statement.

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[1] http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm510251.htm

[2] http://www.bd.com/tripath/products/outside_us/outside_us_sp.asp

[3] http://www.cancer.gov/types/cervical/hp